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"Pfeffer, Mike"
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Bangkok dangerous
\"Original Bangkok Dangerous directors Danny and Oxide Pang return to familiar territory with this remake of their own popular 1999 thriller about a ruthless hitman (Nicolas Cage) who travels to Bangkok in order to carry out four crucial jobs. During the course of his missions, the triggerman falls in love with a pretty local girl while also forming a friendly bond with his young errand boy\"--Allmovie.com, viewed November 21, 2017.
DVD
MedHELM: Holistic Evaluation of Large Language Models for Medical Tasks
While large language models (LLMs) achieve near-perfect scores on medical licensing exams, these evaluations inadequately reflect the complexity and diversity of real-world clinical practice. We introduce MedHELM, an extensible evaluation framework for assessing LLM performance for medical tasks with three key contributions. First, a clinician-validated taxonomy spanning 5 categories, 22 subcategories, and 121 tasks developed with 29 clinicians. Second, a comprehensive benchmark suite comprising 35 benchmarks (17 existing, 18 newly formulated) providing complete coverage of all categories and subcategories in the taxonomy. Third, a systematic comparison of LLMs with improved evaluation methods (using an LLM-jury) and a cost-performance analysis. Evaluation of 9 frontier LLMs, using the 35 benchmarks, revealed significant performance variation. Advanced reasoning models (DeepSeek R1: 66% win-rate; o3-mini: 64% win-rate) demonstrated superior performance, though Claude 3.5 Sonnet achieved comparable results at 40% lower estimated computational cost. On a normalized accuracy scale (0-1), most models performed strongly in Clinical Note Generation (0.73-0.85) and Patient Communication & Education (0.78-0.83), moderately in Medical Research Assistance (0.65-0.75), and generally lower in Clinical Decision Support (0.56-0.72) and Administration & Workflow (0.53-0.63). Our LLM-jury evaluation method achieved good agreement with clinician ratings (ICC = 0.47), surpassing both average clinician-clinician agreement (ICC = 0.43) and automated baselines including ROUGE-L (0.36) and BERTScore-F1 (0.44). Claude 3.5 Sonnet achieved comparable performance to top models at lower estimated cost. These findings highlight the importance of real-world, task-specific evaluation for medical use of LLMs and provides an open source framework to enable this.
Paper
malariaAtlas: an R interface to global malariometric data hosted by the Malaria Atlas Project
Background
The Malaria Atlas Project (MAP) has worked to assemble and maintain a global open-access database of spatial malariometric data for over a decade. This data spans various formats and topics, including: geo-located surveys of malaria parasite rate; global administrative boundary shapefiles; and global and regional rasters representing the distribution of malaria and associated illnesses, blood disorders, and intervention coverage. MAP has recently released
malariaAtlas,
an R package providing a direct interface to MAP’s routinely-updated malariometric databases and research outputs.
Methods and results
The current paper reviews the functionality available in
malariaAtlas
and highlights its utility for spatial epidemiological analysis of malaria.
malariaAtlas
enables users to freely download, visualise and analyse global malariometric data within R. Currently available data types include: malaria parasite rate and vector occurrence point data; subnational administrative boundary shapefiles; and a large suite of rasters covering a diverse range of metrics related to malaria research.
malariaAtlas
is here used in two mock analyses to illustrate how this data may be incorporated into a standard R workflow for spatial analysis.
Conclusions
malariaAtlas
is the first open-access R-interface to malariometric data, providing a new and reproducible means of accessing such data within a freely available and commonly used statistical software environment. In this way, the
malariaAtlas
package aims to contribute to the environment of data-sharing within the malaria research community.
Journal Article
Enforced viral replication activates adaptive immunity and is essential for the control of a cytopathic virus
Type 1 interferon limits virus replication. Lang and colleagues show that expression of Usp18 in metallophilic macrophages results in less interferon responsiveness, which allows locally restricted virus replication and the induction of adaptive immune responses.
The innate immune system limits viral replication via type I interferon and also induces the presentation of viral antigens to cells of the adaptive immune response. Using infection of mice with vesicular stomatitis virus, we analyzed how the innate immune system inhibits viral propagation but still allows the presentation of antigen to cells of the adaptive immune response. We found that expression of the gene encoding the inhibitory protein Usp18 in metallophilic macrophages led to lower type I interferon responsiveness, thereby allowing locally restricted replication of virus. This was essential for the induction of adaptive antiviral immune responses and, therefore, for preventing the fatal outcome of infection. In conclusion, we found that enforced viral replication in marginal zone macrophages was an immunological mechanism that ensured the production of sufficient antigen for effective activation of the adaptive immune response.
Journal Article
Gradual caldera collapse at Bárdarbunga volcano, Iceland, regulated by lateral magma outflow
Volcanic eruptions occur frequently, but only rarely are they large enough to cause the top of the mountain to collapse and form a caldera. Gudmundsson et al. used a variety of geophysical tools to monitor the caldera formation that accompanied the 2014 Bárdarbunga volcanic eruption in Iceland. The volcanic edifice became unstable as magma from beneath Bárdarbunga spilled out into the nearby Holuhraun lava field. The timing of the gradual collapse revealed that it is the eruption that drives caldera formation and not the other way around. Science , this issue p. 262 Magma flow from under the Bárdarbunga volcano drove caldera collapse during the 2014 eruption. Large volcanic eruptions on Earth commonly occur with a collapse of the roof of a crustal magma reservoir, forming a caldera. Only a few such collapses occur per century, and the lack of detailed observations has obscured insight into the mechanical interplay between collapse and eruption. We use multiparameter geophysical and geochemical data to show that the 110-square-kilometer and 65-meter-deep collapse of Bárdarbunga caldera in 2014–2015 was initiated through withdrawal of magma, and lateral migration through a 48-kilometers-long dike, from a 12-kilometers deep reservoir. Interaction between the pressure exerted by the subsiding reservoir roof and the physical properties of the subsurface flow path explain the gradual, near-exponential decline of both collapse rate and the intensity of the 180-day-long eruption.
Journal Article
Ground-Based Measurements of the 2014–2015 Holuhraun Volcanic Cloud (Iceland)
The 2014–2015 Bárðarbunga fissure eruption at Holuhraun in central Iceland was distinguished by the high emission of gases, in total 9.6 Mt SO2, with almost no tephra. This work collates all ground-based measurements of this extraordinary eruption cloud made under particularly challenging conditions: remote location, optically dense cloud with high SO2 column amounts, low UV intensity, frequent clouds and precipitation, an extensive and hot lava field, developing ramparts, and high-latitude winter conditions. Semi-continuous measurements of SO2 flux with three scanning DOAS instruments were augmented by car traverses along the ring-road and along the lava. The ratios of other gases/SO2 were measured by OP-FTIR, MultiGAS, and filter packs. Ratios of SO2/HCl = 30–110 and SO2/HF = 30–130 show a halogen-poor eruption cloud. Scientists on-site reported extremely minor tephra production during the eruption. OPC and filter packs showed low particle concentrations similar to non-eruption cloud conditions. Three weather radars detected a droplet-rich eruption cloud. Top of eruption cloud heights of 0.3–5.5 km agl were measured with ground- and aircraft-based visual observations, web camera and NicAIR II infrared images, triangulation of scanning DOAS instruments, and the location of SO2 peaks measured by DOAS traverses. Cloud height and emission rate measurements were critical for initializing gas dispersal simulations for hazard forecasting.
Journal Article
Adult-onset spinocerebellar ataxia syndromes due to MTATP6 mutations
BackgroundSpinocerebellar ataxia syndromes presenting in adulthood have a broad range of causes, and despite extensive investigation remain undiagnosed in up to ∼50% cases. Mutations in the mitochondrially encoded MTATP6 gene typically cause infantile-onset Leigh syndrome and, occasionally, have onset later in childhood. The authors report two families with onset of ataxia in adulthood (with pyramidal dysfunction and/or peripheral neuropathy variably present), who are clinically indistinguishable from other spinocerebellar ataxia patients.MethodsGenetic screening study of the MTATP6 gene in 64 pedigrees with unexplained ataxia, and case series of two families who had MTATP6 mutations.ResultsThree pedigrees had mutations in MTATP6, two of which have not been reported previously and are detailed in this report. These families had the m.9185T>C and m.9035T>C mutations, respectively, which have not previously been associated with adult-onset cerebellar syndromes. Other investigations including muscle biopsy and respiratory chain enzyme activity were non-specific or normal.ConclusionsMTATP6 sequencing should be considered in the workup of undiagnosed ataxia, even if other investigations do not suggest a mitochondrial DNA disorder.
Journal Article
Teaching Young Adult Literature: Why Should We Have All the Fun? Encouraging Colleagues to Read YA Novels across the Curriculum
Teaching Young Adult Literature describes innovative methods for engaging students in reading, writing, and discussing contemporary and classic literary texts written for adolescents.
Journal Article
